Does Keppra (levetiracetam) have a sedative effect?

Does Keppra Have a Sedative Effect?

Yes, levetiracetam (Keppra) does have sedative effects, with somnolence being one of the most frequently reported adverse events, occurring in 12-23% of patients in clinical trials. 1

Evidence from FDA Labeling and Clinical Trials

The FDA-approved drug label for levetiracetam clearly identifies somnolence as a common adverse effect:

• Somnolence occurred in 15% of adult patients with partial onset seizures treated with levetiracetam compared to 8% on placebo 1
• In pediatric patients (ages 4-16), somnolence occurred in 23% of those treated with levetiracetam versus 11% on placebo 1
• In patients with myoclonic seizures, somnolence was reported in 12% of levetiracetam-treated patients compared to 2% on placebo 1

Clinical Context and Severity

The sedative effect of levetiracetam is generally mild to moderate in intensity and is dose-dependent 1, 2:

• Higher doses (2000 mg/day) may produce more sedation than lower doses (1000 mg/day) 2
• In overdose cases, levetiracetam causes significant sedation and respiratory depression requiring intubation, though recovery is rapid with supportive care 3

Comparison to Other Antiepileptic Drugs

Levetiracetam's sedative profile is notably milder than traditional sedating antiepileptics like benzodiazepines or barbiturates:

• Unlike benzodiazepines (midazolam, lorazepam), levetiracetam does not cause the same degree of respiratory depression or cardiovascular instability at therapeutic doses 4
• The sedation does not appear to worsen significantly with chronic use, and no tolerance development to the sedative effect has been reported 5

Clinical Use in Sedation Protocols

Levetiracetam is NOT used as a primary sedative agent but is recognized for having antiepileptic effects in sedated patients:

• Guidelines note that sedatives like propofol and benzodiazepines routinely used in post-cardiac arrest patients have antiepileptic effects, but levetiracetam is used specifically for seizure control, not sedation 4
• When treating status epilepticus, levetiracetam (30 mg/kg IV) is recommended as a second-line antiseizure medication with 68-73% efficacy and minimal adverse effects including sedation 6

Important Clinical Considerations

The sedative effect should be anticipated but is rarely severe enough to require discontinuation:

• Only one case requiring discontinuation due to side effects was reported in a study of 31 pharmacoresistant epilepsy patients 7
• The sedation typically does not interfere with neurological assessment when used appropriately 4
• Avoid combining levetiracetam with other CNS depressants without careful monitoring, as additive sedative effects may occur 1

Practical Management

When prescribing levetiracetam, counsel patients that:

• Somnolence is common (15-23% of patients) but usually mild and may improve with continued use 1
• Patients should avoid driving or operating machinery until they know how the medication affects them 1
• The sedative effect is less pronounced than with benzodiazepines or barbiturates, making it a favorable option when sedation is a concern 4, 6